Usage
Dehydroemetine is prescribed for the treatment of amebiasis, specifically amebic dysentery and amebic liver abscess. It is classified as an antiprotozoal agent, specifically an amebicide. Its mechanism of action involves inhibiting protein synthesis by blocking the translocation of tRNA-amino acid complex within the ribosome, effectively killing the trophozoites (active form) of Entamoeba histolytica. It is ineffective against the cyst form.
Alternate Names
Dehydroemetine hydrochloride, DHE. A brand name is Tilemetin.
How It Works
Pharmacodynamics: Dehydroemetine acts primarily on the trophozoites of Entamoeba histolytica by inhibiting protein synthesis. It binds to the ribosomes of the parasite, interfering with the movement of tRNA and amino acids, thereby halting protein production and leading to parasite death. This targeted action minimizes its effects on human cells.
Pharmacokinetics:
- Absorption: Dehydroemetine is poorly absorbed orally and therefore administered intramuscularly (IM).
- Distribution: It is distributed widely in the body, achieving therapeutic concentrations in various tissues, including the liver.
- Metabolism: Limited information available. It is a synthetic analog of emetine, with possibly similar metabolism.
- Excretion: Primarily renal excretion, with some hepatic metabolism.
Mode of Action: Inhibition of protein synthesis via ribosome binding. It arrests the intra-ribosomal translocation of the tRNA-amino acid complex, which effectively shuts down protein production in the parasite.
Receptor Binding/Enzyme Inhibition: Dehydroemetine directly targets the parasite’s ribosomes, specifically interfering with the protein synthesis machinery. There is no known receptor binding or enzyme inhibition in human cells.
Dosage
Standard Dosage
Adults:
1 mg/kg body weight daily (IM), up to a maximum of 60 mg, for 4-6 days.
Children:
1 mg/kg body weight daily (IM) for no more than 5 days. Pediatric safety considerations necessitate careful monitoring for adverse effects.
Special Cases:
- Elderly Patients: Reduce the dose by up to 50% due to potential age-related decline in organ function.
- Patients with Renal Impairment: Dosage adjustment is recommended, based on the degree of impairment, but specific guidelines vary depending on the severity of renal dysfunction.
- Patients with Hepatic Dysfunction: Dosage adjustment might be required but specific recommendations vary based on the level of dysfunction. Close monitoring is advised.
- Patients with Comorbid Conditions: Exercise caution with concurrent cardiovascular disease. Adjust dosage based on the individual patient’s clinical status.
Clinical Use Cases
Dehydroemetine is typically not used in the context of procedures like intubation, surgical procedures, mechanical ventilation, or routinely in the ICU or emergency situations. Its primary use is in the treatment of amebiasis that doesn’t respond to first-line treatments. It is specifically indicated for amebic dysentery and amebic liver abscess. In these instances, the standard dosage guidelines apply.
Dosage Adjustments
Dosage adjustments are necessary for elderly patients and those with renal or hepatic impairment. Specific modifications should be made based on the individual’s clinical condition and the severity of organ dysfunction.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, headache, weakness, local pain at the injection site, and abdominal cramps.
Rare but Serious Side Effects
Cardiotoxicity (hypotension, tachycardia, arrhythmias, ECG changes, myocarditis), neuromuscular effects (muscle pain and weakness, especially in the limbs and neck; shortness of breath), dizziness, and fever.
Long-Term Effects
Prolonged use can lead to neuromuscular toxicity and cardiotoxicity, necessitating careful monitoring and limiting the duration of treatment.
Adverse Drug Reactions (ADR)
Cardiotoxicity and neuromuscular toxicity are the most significant ADRs and require immediate discontinuation of the drug and supportive care.
Contraindications
Absolute contraindications include hypersensitivity to dehydroemetine, pre-existing heart disease (including congestive heart failure, recent myocardial infarction, and arrhythmias), polyneuritis (nerve damage), and pregnancy. Relative contraindications include renal or hepatic impairment and neuromuscular disorders. It is crucial to exercise extreme caution in individuals with these conditions.
Drug Interactions
Dehydroemetine can interact with drugs that prolong the QT interval, increasing the risk of cardiac arrhythmias. Caution is warranted when using it concurrently with other cardiotoxic drugs like beta-blockers, calcium channel blockers, and certain antiarrhythmics. Concomitant use with other medications metabolized by the liver may alter drug levels and necessitate dosage adjustments. It is essential to obtain a complete medication history from the patient, including OTC drugs and supplements.
Pregnancy and Breastfeeding
Dehydroemetine is contraindicated in pregnancy due to its potential fetal toxicity (Pregnancy Category C). It should only be used in life-threatening situations where the benefits outweigh the substantial risks. It is not known whether dehydroemetine is excreted in breast milk. However, due to the potential for serious adverse effects in nursing infants, breastfeeding is contraindicated during treatment.
Drug Profile Summary
- Mechanism of Action: Inhibits protein synthesis in Entamoeba histolytica by blocking tRNA translocation.
- Side Effects: Nausea, vomiting, diarrhea, headache, pain at injection site; rarely: cardiotoxicity, neuromuscular toxicity.
- Contraindications: Heart disease, polyneuritis, pregnancy, breastfeeding.
- Drug Interactions: Drugs that prolong the QT interval, other cardiotoxic drugs.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 1 mg/kg IM daily (max 60 mg) for 4-6 days in adults; 1 mg/kg IM daily for no more than 5 days in children. Adjust dosage in elderly patients and those with hepatic/renal impairment.
- Monitoring Parameters: ECG, cardiac function, neuromuscular function, liver and kidney function tests.
Popular Combinations
Dehydroemetine is sometimes used in combination with a luminal amebicide like diloxanide furoate or tetracycline to ensure complete eradication of amebiasis. Tetracycline is used to prevent bacterial superinfection in cases of amebic dysentery. Chloroquine may be added for hepatic amebiasis.
Precautions
- General Precautions: Cardiac and neuromuscular monitoring.
- Specific Populations: Avoid in pregnancy and breastfeeding. Adjust dose in elderly and those with organ dysfunction.
- Lifestyle Considerations: No specific lifestyle recommendations.
FAQs
Q1: What is the recommended dosage for Dehydroemetine?
A: Adults: 1 mg/kg IM daily (max 60 mg) for 4-6 days. Children: 1 mg/kg IM daily for a maximum of 5 days. Dose adjustments needed for elderly patients and those with renal or hepatic impairment.
Q2: What is the route of administration for Dehydroemetine?
A: Intramuscular (IM) injection only. Intravenous administration is contraindicated.
Q3: What are the most serious side effects of Dehydroemetine?
A: Cardiotoxicity (hypotension, arrhythmias, myocarditis) and neuromuscular toxicity (muscle pain, weakness, shortness of breath).
Q4: Can Dehydroemetine be used during pregnancy?
A: No, it is contraindicated in pregnancy due to potential fetal toxicity.
Q5: How does Dehydroemetine work?
A: It inhibits protein synthesis in the Entamoeba histolytica parasite.
Q6: What are the contraindications to using Dehydroemetine?
A: Heart disease, polyneuritis, pregnancy, and breastfeeding. Caution advised with renal or hepatic impairment.
Q7: What other medications interact with Dehydroemetine?
A: Drugs that prolong the QT interval or cause cardiotoxicity.
Q8: What should be monitored in patients taking Dehydroemetine?
A: Cardiac function (ECG, blood pressure), neuromuscular function, liver and kidney function tests.
Q9: What infections is Dehydroemetine used to treat?
A: Amebiasis (specifically amebic dysentery and amebic liver abscess).
Q10: Why is Dehydroemetine given intramuscularly?
A: It’s poorly absorbed orally and can cause local irritation. IM administration provides optimal delivery.
